Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase

Yuichi Sekine, Satoshi Tsuji, Osamu Ikeda, Kenji Sugiyma, Kenji Oritani, Kazuya Shimoda, Ryuta Muromoto, Norihiko Ohbayashi, Akihiko Yoshimura, Tadashi Matsuda

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.

Original languageEnglish
Pages (from-to)2397-2407
Number of pages11
JournalJournal of Immunology
Volume179
Issue number4
Publication statusPublished - 2007 Aug 15
Externally publishedYes

Fingerprint

Signal Transducing Adaptor Proteins
Focal Adhesion Protein-Tyrosine Kinases
Cell Adhesion
Integrins
Proteolysis
T-Lymphocytes
Fibronectins
Proteins
Proteasome Inhibitors
Jurkat Cells
Ubiquitin-Protein Ligases

ASJC Scopus subject areas

  • Immunology

Cite this

Sekine, Y., Tsuji, S., Ikeda, O., Sugiyma, K., Oritani, K., Shimoda, K., ... Matsuda, T. (2007). Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase. Journal of Immunology, 179(4), 2397-2407.

Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase. / Sekine, Yuichi; Tsuji, Satoshi; Ikeda, Osamu; Sugiyma, Kenji; Oritani, Kenji; Shimoda, Kazuya; Muromoto, Ryuta; Ohbayashi, Norihiko; Yoshimura, Akihiko; Matsuda, Tadashi.

In: Journal of Immunology, Vol. 179, No. 4, 15.08.2007, p. 2397-2407.

Research output: Contribution to journalArticle

Sekine, Y, Tsuji, S, Ikeda, O, Sugiyma, K, Oritani, K, Shimoda, K, Muromoto, R, Ohbayashi, N, Yoshimura, A & Matsuda, T 2007, 'Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase', Journal of Immunology, vol. 179, no. 4, pp. 2397-2407.
Sekine, Yuichi ; Tsuji, Satoshi ; Ikeda, Osamu ; Sugiyma, Kenji ; Oritani, Kenji ; Shimoda, Kazuya ; Muromoto, Ryuta ; Ohbayashi, Norihiko ; Yoshimura, Akihiko ; Matsuda, Tadashi. / Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase. In: Journal of Immunology. 2007 ; Vol. 179, No. 4. pp. 2397-2407.
@article{569877df80824eae905bdf07d85ba923,
title = "Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase",
abstract = "Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.",
author = "Yuichi Sekine and Satoshi Tsuji and Osamu Ikeda and Kenji Sugiyma and Kenji Oritani and Kazuya Shimoda and Ryuta Muromoto and Norihiko Ohbayashi and Akihiko Yoshimura and Tadashi Matsuda",
year = "2007",
month = "8",
day = "15",
language = "English",
volume = "179",
pages = "2397--2407",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase

AU - Sekine, Yuichi

AU - Tsuji, Satoshi

AU - Ikeda, Osamu

AU - Sugiyma, Kenji

AU - Oritani, Kenji

AU - Shimoda, Kazuya

AU - Muromoto, Ryuta

AU - Ohbayashi, Norihiko

AU - Yoshimura, Akihiko

AU - Matsuda, Tadashi

PY - 2007/8/15

Y1 - 2007/8/15

N2 - Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.

AB - Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.

UR - http://www.scopus.com/inward/record.url?scp=34848915422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848915422&partnerID=8YFLogxK

M3 - Article

C2 - 17675501

AN - SCOPUS:34848915422

VL - 179

SP - 2397

EP - 2407

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -